POS0723 ANALYSES OF PLASMA METABOLIC PROTEINS REVEAL BIOMARKERS PREDICTIVE OF SUBSEQUENT DEVELOPMENT OF GIANT CELL ARTERITIS; A PROSPECTIVE STUDY
Authors: K. Wadström, L. T. H. Jacobsson, A. J. Mohammad, K. J. Warrington, E. Matteson, M. Jakobsson, C. Turesson
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Incident cases of of giant cell arteritis (GCA) have a significantly reduced prevalence of diabetes at time of diagnosis (1) and lower fasting blood glucose, lipid levels and body mass index compared to controls have been found years before clinical diagnosis [2,3]. This implicates metabolic pathways in the development of GCA. <h3>Objectives</h3> To investigate the relation between plasma proteins associated with metabolism and subsequent development of GCA. <h3>Methods</h3> Participants in a population-based survey (N=30447), who were subsequently diagnosed with GCA, were identified in a structured process. GCA-free controls, matched for sex, year of birth, and year of screening were selected from the study cohort. Baseline plasma samples were analyzed using the antibody-based OLINK proteomics metabolism panel (92 proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explain the variance in the proteome. <h3>Results</h3> There were 95 cases with a confirmed incident diagnosis of GCA (median 11.4 years after inclusion). Among biomarkers with a priori hypotheses, Adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated and Fructose-1,6-bisphosphatase 1 (FBP1) negatively associated with subsequent GCA (Table 1). In particular, ADGRE2 levels were elevated compared to controls in the subset sampled &lt;8.5 years before diagnosis (Table 1). For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those sampled closest to diagnosis, with a decreasing trend with longer time to GCA (p=0.03). In the hypothesis generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA. <h3>Conclusion</h3> Our results indicate that changes in levels of plasma proteins that have regulatory effects on the immune system might precede clinical onset of GCA by many years. Among the biomarkers found to be predictive of subsequent GCA, both Metrnl and ADGRE2 are associated with macrophage activation. ROR1 mediated activation of NFkB may be relevant in this context. The negative association with FBP1, which is a rate-controlling enzyme in the gluconeogenic pathway, is compatible with a protective role for glucose metabolites. <h3>References</h3> [1]Ungpresart P et al. Mod Rheumatol. 2016;26(3):410-4 [2]Wadström K et al. Rheumatology (Oxford) 2020;<b>59</b>(11):3229-36 [3]Jakobsson K et al. Rheumatology (Oxford) 2015;<b>54</b>(3):433-40 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Karin Wadström: None declared, Lennart T.H. Jacobsson Consultant of: personal fees from from Novartis, Eli-Lily and Janssen, Aladdin J Mohammad: None declared, Kenneth J Warrington Consultant of: personal fees from Chemocentryx, Grant/research support from: Support from Eli-Lilly, GSK and Kiniksa to the Mayo Clinic for clinical trials, Eric Matteson Consultant of: UpToDate, Magnus Jakobsson: None declared, Carl Turesson Speakers bureau: AbbVie, BMS, Nordic Drugs, Pfizer och Roche, Consultant of: Roche, Grant/research support from: research grant paid to Lund University from Bristol Myers-Squibb.